A Role for Interleukin-10 in the Murine Model of Lyme Disease
Lyme disease is caused by persistent infection with the bacterium Borrelia burgdorferi (Bb) and includes a multisystem disease characterized by periodic inflammation. As it is an obligate parasite, Bb has evolved various strategies to persist for extended times within mammalian and tick hosts. It is largely unknown which immune mediators are important for controlling this spirochete. We have discovered that Interleukin-10- deficient (IL-10-/-) mice exhibit up to 10-fold greater clearance of Bb from target tissues compared to wild type mice, establishing IL-10 as the only cytokine currently known to have such a significant effect on spirochetal clearance. The goals of this work were to identify murine defense mechanisms dysregulated by IL-10 and describe specific effects on Bb clearance. Although increases in Bb-specific antibody by two weeks post infection were noted in IL-10-/- mice compared to wild type controls, these antibodies were not solely responsible for enhanced clearance of Bb. Instead, we demonstrate enhanced innate immune responses in IL-10-/- mice as being important to increased clearance of this spirochete. Upregulation of IL-10 transcript levels in skin harvested early during Bb infection also suggested this cytokine suppression could occur in vivo. We developed a novel in vitro co-culture system to assess Bb-macrophage interactions, which allowed us to show that Bb can elicit rapid and substantial IL-10 production by macrophages, which are significant in that they are resident in skin tissues and direct inflammatory responses. Finally, we illustrate that IL-10 produced by macrophages can act in an autocrine loop to suppress subsequent inflammatory responses that are necessary to promote efficient immune clearance of Bb. These studies have laid the ground work to allow delineation of 169 the host cell types that produce and/or respond to Bb-elicited IL-10, which can hopefully lead to curative treatments of Lyme disease.
School:University of Toledo Health Science Campus
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:lyme disease macrophages interleukin 10 borrelia burgdorferi innate immune responses suspension of clearance
Date of Publication:01/01/2007